Method for the preparation of 1-deoxy baccatin III, 1-deoxy taxol and 1-deoxy taxol analogs

ABSTRACT

1-Deoxybaccatin III, 1-deoxytaxol and 1-deoxy taxol analogs and method for the preparation thereof.

REFERENCE TO RELATED APPLICATION

[0001] This application claims priority, at least in part, fromProvisional Application Serial No. 60/016,927, filed May 6, 1996.

[0002] This invention was made with Government support under NIH Grant#CA 42031 awarded by the National Institutes of Health. The Governmenthas certain rights in the invention.

BACKGROUND OF THE INVENTION

[0003] The present invention is directed to novel taxanes which haveutility as antitumor agents and to a process for their preparation.

[0004] The taxane family of terpenes, of which baccatin III and taxolare members, has attracted considerable interest in both the biologicaland chemical arts. Taxol is a promising cancer chemotherapeutic agentwith a broad spectrum of tumor-inhibiting activity. Taxol has a 2′R, 3′Sconfiguration and the following structural formula:

[0005] wherein Ac is acetyl. Because of this promising activity, taxolis currently undergoing clinical trials in both France and the UnitedStates.

[0006] Colin et al. reported in U.S. Pat. No. 4,814,470 that taxolderivatives having the structural formula (II) below, have an activitysignificantly greater than that of taxol (I).

[0007] R′ represents hydrogen or acetyl and one of R″ and R′″ representshydroxy and the other represents tert-butoxycarbonylamino and theirstereoisomeric forms, and mixtures thereof. The compound of this formulain which R″ is hydroxy, R′″ is tert-butoxycarbonylamino having the 2′R,3′S configuration is commonly referred to as taxotere.

[0008] Although taxol and taxotere are promising chemotherapeuticagents, they are not universally effective. Accordingly, a need remainsfor additional chemotherapeutic agents.

SUMMARY OF THE INVENTION

[0009] Among the objects of the present invention, therefore, is theprovision of novel taxanes which are valuable anti-tumor agents and aprocess for their preparation.

[0010] Briefly, therefore, the present invention is directed to aprocess for the preparation of 1-deoxy baccatin III, 1-deoxy taxol and1-deoxy taxol analogs. The process comprises at least one of thefollowing steps:

[0011] (a) reacting a compound having the formula:

[0012] with a peracid such as metachloroperbenzoic acid to form acompound having the formula:

[0013] wherein P₁₀ is a silyl hydroxy protecting group such astriethylsilyl or an acyl group such as benzoyl. In this reaction, theprotected hydroxy group —OP₁₀ migrates to the adjacent carbon andbecomes —OP₉ with P₉ being the same as P₁₀;

[0014] (b) subjecting a compound having the formula:

[0015] to an epoxy alcohol fragmentation consisting of (ia) epoxidationof an olefinic residue with a hydroperoxide, preferably t-BuOOH, in thepresence of a transition metal catalyst, preferably titaniumtetraisopropoxide, or (ib) treatment of the olefinic residue with aperacid such as peracetic acid followed by (ii) addition of a sulfide,preferably dimethyl sulfide, followed by heating in the presence of atransition metal catalyst, preferably titanium tetraisopropoxide, toform a compound having the formula:

[0016] wherein P₉ is a hydroxyl protecting group such as a silyl group,ketal, acetal, or ether which does not contain a reactive functionality;

[0017] (c) reacting a compound having the formula:

[0018] with a vinyl organometallic reagent to form a compound having theformula:

[0019] (d) reacting a compound having the formula:

[0020] with a paladium catalyst to form a compound having the formula:

[0021] (e) reacting a compound having the formula:

[0022] with a base, most preferably BaO in methanol, and protecting theC7 hydroxy substituent, for example, by reacting the product withTESOTf, to form a compound having the formula:

[0023] (f) reacting a compound having the formula:

[0024] with SeO₂ to form a compound having the formula:

[0025] wherein E₇ is hydrogen or a hydroxy protecting group, and P₂, P₇,P₉, P₁₀ and P₁₃ are hydroxy protecting groups as hereinafter defined.

[0026] In general, the process of the present invention may be used toprepare 1-deoxy baccatin III, 1-deoxy taxol and 1-deoxy taxol analogshaving the formula:

[0027] wherein

[0028] M comprises ammonium or is a metal;

[0029] R₂ is —OT₂, —OCOZ₂, or —OCOOZ₂;

[0030] R₄ is —OT₄, —OCOZ₄, or —OCOOZ₄;

[0031] R₆ is hydrogen, keto, —OT₆, —OCOZ₆ or —OCOOZ₆;

[0032] R₇ is hydrogen, halogen, —OT₇, —OCOZ₇ or —OCOOZ₇;

[0033] R₉is hydrogen, keto, —OT₉, —OCOZ₉ or —OCOOZ₉;

[0034] R₁₀ is hydrogen, keto, —OT₁₀, —OCOZ₁₀ or —OCOOZ₁₀;

[0035] R₆, R₇, R₉, and R₁₀ independently have the alpha or betastereochemical configuration;

[0036] R₁₃ is hydroxy, protected hydroxy, keto, MO— or

[0037] T₂, T₄, T₆, T₇, T₉ and T₁₀ are independently hydrogen or hydroxyprotecting group;

[0038] X₁ is —OX₆;

[0039] X₂ is hydrogen, hydrocarbon, heterosubstituted hydrocarbon, orheteroaryl;

[0040] X₃ and X₄ are independently hydrogen, hydrocarbon,heterosubstituted hydrocarbon, or heteroaryl;

[0041] X₅ is —COX₁₀, —COOX₁₀, —COSX₁₀, or —CONX₈X₁₀;

[0042] X₆ is hydrogen, hydrocarbon, heterosubstituted hydrocarbon,heteroaryl, or hydroxy protecting group or a functional group whichincreases the water solubility of the taxane derivative;

[0043] X₈ is hydrogen, hydrocarbon, heterosubstituted hydrocarbon;

[0044] X₁₀ is hydrocarbon, heterosubstituted hydrocarbon, or heteroaryl;and

[0045] Z₂, Z₄, Z₆, Z₇, Z₉ and Z₁₀ are independently hydrocarbon,heterosubstituted hydrocarbon, or heteroaryl.

[0046] The present invention is additionally directed to compoundshaving the formulae

[0047] wherein E₇ is hydrogen or a hydroxy protecting group; Bz isbenzoyl; P₂, P₃, P₇, P₉, P₁₀ and P₁₃ are hydroxy protecting groups; andR₁₃ is as previously defined. These compounds are key intermediates inthe synthesis of 1-deoxy baccatin III, 1-deoxy taxol and other analogs.The present invention is also directed to processes for the preparationof these key intermediates.

[0048] Other objects and features of this invention will be in partapparent and in part pointed out hereinafter.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0049] The process of the present invention enables the preparation of1-deoxy taxol, 1-deoxy taxotere and analogs of 1-deoxy taxol and 1-deoxytaxotere from 1-deoxy baccatin III, 1-deoxy-10-deactylbaccatin III, oranalogs thereof. In a preferred embodiment, these compounds have theformula:

[0050] wherein

[0051] M comprises ammonium or is a metal;

[0052] R₂ is —OCOZ₂;

[0053] R₄ is —OCOZ₄;

[0054] R₆ is hydrogen;

[0055] R₇ is hydrogen, —OT₇, or —OCOZ₇;

[0056] R₉ is hydrogen, keto, —OT₉, —OCOZ₉;

[0057] R₁₀ is hydrogen, keto, —OT₁₀, or —OCOZ₁₀;

[0058] R₁₃ is MO— or

[0059] T₇, T₉ and T₁₀ are independently hydrogen or hydroxy protectinggroup;

[0060] X₁ is —OX₆;

[0061] X₂ is hydrogen;

[0062] X₃ is alkyl, substituted alkyl, alkenyl, substituted alkenyl,alkynyl, substituted alkynyl, aryl, substituted aryl, or heteroaryl;

[0063] X₄ is hydrogen;

[0064] X₅ is —COX₁₀ or —COOX₁₀;

[0065] X₆ is hydrogen or hydroxy protecting group;

[0066] X₁₀ is alkyl, substituted alkyl, alkenyl, substituted alkenyl,alkynyl, substituted alkynyl, phenyl, substituted phenyl, or heteroaryl;and

[0067] Z₂ is alkyl, substituted alkyl, phenyl, substituted phenyl, orheteroaryl;

[0068] Z₄ is phenyl, substituted phenyl, or heteroaryl; and

[0069] Z₇, Z₉ and Z₁₀ are independently alkyl, substituted alkyl,phenyl, substituted phenyl, or heteroaryl.

[0070] An exemplary synthesis of 1-deoxy baccatin III is depicted inReaction Scheme 1. The starting material, diol 1, can be prepared frompatchino (commonly known as B-patchouline epoxide) which is commerciallyavailable. The patchino is first reacted with an organo-metallic, suchas lithium t-butyl followed by oxidation with an organic peroxide, suchas t-butylperoxide in the presence of titanium tetraisopropoxide to forma tertiary alcohol. The tertiary alcohol is then reacted with a Lewisacid, such as boron trifluoride at low temperature, in the range from40° C. to −100° C.; in the presence of an acid, such as trifluoromethanesulfonic acid. A graphical depiction of this reaction scheme along withan experimental write-up for the preparation of diol 1 can be found inU.S. Pat. No. 4,876,399.

[0071] In this reaction scheme, P₂ is BOM; P₃ is TMS; P₇ is Ac incompounds 12-15 and TES in compounds 18-23; P₉ is TES in compounds 4, 5,6 and 7, and TMS in compounds 8, 9, 10, 11 and 12; P₁₀ is TES, and P₁₃is TBS in compounds 7 through 21 and TES in compounds 22 and 23. Itshould be understood, however, that P₂, P₃, P₇, P₉, P₁₀, and P₁₃ may beother hydroxy protecting groups.

[0072] In general, tetracyclic taxanes bearing C13 side chains may beobtained by reacting a β-lactam with alkoxides having the taxanetetracyclic nucleus and a C-13 metallic or ammonium oxide substituent toform compounds having a β-amido ester substituent at C-13. The β-lactamshave the following structural formula:

[0073] wherein X₁-X₅ are as defined above. The alkoxides having thetetracyclic taxane nucleus and a C-13 metallic oxide or ammonium oxidesubstituent have the following structural formula:

[0074] wherein R₂, R₄, R₆, R₇, R₉, R₁₀ and R₁₃ are as previously definedand M comprises ammonium or is a metal optionally selected from GroupIA, IIA, transition (including lanthanides and actinides), IIB, IIIA,IVA, VA, or VIA metals (CAS version). If M comprises ammonium, it ispreferably tetraalkylammonium and the alkyl component of thetetraalkylammonium substituent is preferably C₁-C₁₀ alkyl such as methylor butyl.

[0075] 1-Deoxytaxol may be prepared by protecting the C7 hydroxy groupof 1-deoxy Baccatin III 24 with a suitable hydroxy protecting group,converting the 7-protected Baccatin III to the corresponding alkoxideand reacting the alkoxide with a β-lactam in which X₁ is protectedhydroxy, X₃ is phenyl, X₅ is benzoyl and X₂ and X₄ are hydrogen.Protecting groups such as 2-methoxypropyl (“MOP”), 1-ethoxyethyl (“EE”),benzyloxymethyl are preferred, but a variety of other standardprotecting groups such as trialkyl and triaryl silyl groups may be used.

[0076] 1-Deoxytaxotere may be prepared in the same manner as1-deoxytaxol except that 1-deoxy-10-deacetylbaccatin III is used insteadof 1-deoxybaccatin III and X₅ of the β-lactam is t-butoxycarbonylinstead of benzoyl. 1-deoxy-10-deacetyl-baccatin III may be prepared asset forth in Reaction Scheme 2, starting with compound 22.

[0077] Analogs of 1-deoxy taxol and 1-deoxytaxotere bearing alternativeside chain substituents may be prepared by using other suitablysubstituted β-lactams. For example, 1-deoxy taxol and 1-deoxytaxotereanalogs having alkyl, alkenyl, alkynyl, substituted aryl, heteroaryl orsubstituted heteroaryl substituents at the C3′ position are preparedusing β-lactams in which X₃ is alkyl, alkenyl, alkynyl, substitutedaryl, heteroaryl or substituted heteroaryl. Alternatively, X₅ of theβ-lactam may be —COX₁₀, —COOX₁₀, —COSX₁₀ or —CONX₈X₁₀ wherein X₈ and X₁₀are as previously defined.

[0078] 1-deoxy-10-desacetoxy analogs of taxol can be prepared from thecorresponding 1-deoxy-10-desacetoxy derivatives of baccatin III and1-deoxy-10-desoxy derivatives of 10-DAB. These derivatives may beprepared as illustrated in Reaction Scheme 3 by reacting1-deoxy-baccatin III or 1-deoxy-10-DAB (or their derivatives) withsamarium diiodide. Reaction between the tetracyclic taxane having a C10leaving group and samarium diiodide may be carried out at 0° C. in asolvent such as tetrahydrofuran. Advantageously, the samarium diiodideselectively abstracts the C10 leaving group; C13 side chains and othersubstituents on the tetracyclic nucleus remain undisturbed.

[0079] Analogs of 1-deoxy taxol and 1-deoxytaxotere having alternativeC9 substituents may be prepared by selectively reducing the C9 ketosubstituent of 1-deoxytaxol, 1-deoxy-10-DAB, 1-deoxybaccatin III or oneof the other intermediates disclosed herein to yield the corresponding9-β-hydroxy-1-deoxy derivative. The reducing agent is preferably aborohydride and, most preferably, tetrabutylammoniumboro-hydride(Bu₄NBH₄) or triacetoxyborohydride.

[0080] As illustrated in Reaction Scheme 4, the reaction of1-deoxybaccatin III 24 with Bu₄NBH₄ in methylene chloride yields9-desoxo-9β-hydroxy-1-deoxybaccatin III 25. After the C7 hydroxy groupis protected with a suitable protecting group, a suitable side chain maybe attached to 7-protected-9β-hydroxy-1-deoxy derivative 26 as elsewheredescribed herein. Removal of the remaining protecting groups thus yields9β-hydroxy-desoxo-1-deoxy taxol or other 9-β-hydroxy-1-deoxytetracylictaxane having a C13 side chain.

[0081] Alternatively, the C13 hydroxy group of7-protected-9β-hydroxy-1-deoxy derivative 26 may be protected with aprotecting group which can be selectively removed relative to the C7hydroxy protecting group as illustrated in Reaction Scheme 5, to enablefurther selective manipulation of the various substituents of thetaxane. For example, reaction of 7,13-protected-9β-hydroxy-1-deoxyderivative 27 with KH causes the acetate group to migrate from C10 to C9and the hydroxy group to migrate from C9 to C10, thereby yielding10-desacetyl derivative 28. Protection of the C10 hydroxy group of10-desacetyl derivative 28 with a protecting group yields derivative 29.Selective removal of the C13 hydroxy protecting group from derivative 29yields derivative 30 to which a suitable side chain may be attached asdescribed above.

[0082] As shown in Reaction Scheme 6, 10-oxo derivative 31 can beprovided by oxidation of 10-desacetyl derivative 28. Thereafter, the C13hydroxy protecting group can be selectively removed followed byattachment of a side chain as described above to yield9-acetoxy-10-oxo-taxol or other 9-acetoxy-10-oxotetracylic taxaneshaving a C13 side chain. Alternatively, the C9 acetate group can beselectively removed by reduction of 10-oxo derivative 31 with a reducingagent such as samarium diiodide to yield 9-desoxo-10-oxo derivative 32from which the C13 hydroxy protecting group can be selectively removedfollowed by attachment of a side chain as described above to yield9-desoxo-10-oxo-1-deoxytaxol or other 9-desoxo-10-oxo-1-deoxytetracylictaxanes having a C13 side chain.

[0083] Reaction Scheme 7 illustrates a reaction in which 1-deoxy-10-DABis reduced to yield tetraol 33. The C7 and C10 hydroxyl groups oftetraol 33 can then be selectively protected with a protecting group toproduce diol 34 to which a C13 side chain can be attached as describedabove or, alternatively, after further modification of the tetracylicsubstituents.

[0084] Taxanes having C9 and/or C10 acyloxy substituents other thanacetoxy can be prepared using 1-deoxy-10-DAB as a starting material asillustrated in Reaction Scheme 8. After protecting the C7 hydroxy of1-deoxy-10-DAB with a suitable protecting group to yield 7-protected1-deoxy-10-DAB 35, the C10 hydroxy substituent of 7-protected1-deoxy-10-DAB 35 may then be readily acylated with any standardacylating agent such as an acid chloride to yield derivative 36 having anew C10 acyloxy substituent. Use of the analogous chloroformate insteadof the acid chloride would yield the corresponding carbonate.Deprotection of the C7 hydroxy group, followed by selective reduction ofthe C9 keto substituent of derivative 36 with tetrabutylammoniumborohydride, and then protection of the C7 hydroxy group yields9β-hydroxy derivative 37 to which a C13 side chain may be attached.Alternatively, the C10 and C9 groups can be caused to migrate as setforth in Reaction Scheme 5, above.

[0085] Taxanes having alternative C2 and/or C4 esters can be preparedusing baccatin III and 10-DAB as starting materials. The C2 and/or C4esters of baccatin III and 10-DAB can be selectively reduced to thecorresponding alcohol(s) using reducing agents such as LAH or Red-Al,and new esters can thereafter be substituted using standard acylatingagents such as anhydrides and acid chlorides in combination with anamine such as pyridine, triethylamine, DMAP, or diisopropyl ethyl amine.Alternatively, the C2 and/or C4 alcohols may be converted to new C2and/or C4 esters through formation of the corresponding alkoxide bytreatment of the alcohol with a suitable base such as LDA followed by anacylating agent such as an acid chloride. See, e.g., U.S. Pat. No.5,399,726 which is incorporated herein by reference with respect to thepreparation of taxanes having different C2 and C4 acyloxy substituents.

[0086] In Reaction Scheme 9, 7,10,13-protected 10-DAB 38 is converted tothe diol 39 with lithium aluminum hydride. Deprotonation of diol 39 withLDA followed by reaction with an acid chloride selectively gives the C2ester 40. Deprotonation of the C2 ester 40 with LDA followed by reactionwith acid chloride gives the C2, C4 ester 41. If a chloroformate is usedinstead of the acid chloride, the product is a C2 or C4 carbonate(—OCOOZ₂ or —OCOOZ₄).

[0087] C7 dihydro and other C7 substituted taxanes can be prepared asset forth in Reaction Schemes 10, 11 and 12.

[0088] As shown in Reaction Scheme 11, 1-deoxy-baccatin III may beconverted into 7-fluoro 1-deoxy-baccatin III by treatment with FAR atroom temperature in THF solution. Other 1-deoxy-baccatin derivativeswith a free C7 hydroxyl group behave similarly. Alternatively,7-1-deoxy-chloro baccatin III can be prepared by treatment of baccatinIII with methane sulfonyl chloride and triethylamine in methylenechloride solution containing an excess of triethylamine hydrochloride.

[0089] Taxanes having C7 acyloxy substituents can be prepared as setforth in Reaction Scheme 12. 7,13-protected 10-oxo-derivative 42 isconverted to its corresponding C13 alkoxide by selectively removing theC13 protecting group and replacing it with a metal such as lithium. Thealkoxide is then reacted with a β-lactam or other side chain precursor.Subsequent hydrolysis of the C7 protecting groups causes a migration ofthe C7 hydroxy substituent to C10, migration of the C10 oxo substituentto C9, and migration of the C9 acyloxy substituent to C7.

[0090] 1-deoxy taxanes having alternative C6 substituents can beprepared using the reactions described in Liang et al., TetrahedronLetters, Vol. 36, No. 17, pp. 2901-2904 (1995), starting, however, with1-deoxy-10,13-protected-10-DAB instead of taxol. According to thisreaction scheme, 1-deoxy-10,13-protected-10-DAB is converted to the7-0-triflate using CF₃SO₂Cl. Treatment of the 7-0-triflate with1,8-diazabicyclo(5,4,0)-undec-7-ene (DBU) produces the 7-deoxyintermediate which when reacted with OsO₄ followed by an acid chloride(or chloroformate) yields the corresponding C6 ester or carbonate.

[0091] As used herein, “Ar” means aryl; “Ph” means phenyl; “Bz” meansbenzoyl; “Me” means methyl; “Et” means ethyl; “iPr” means isopropyl;“tBu” and “t-Bu” means tert-butyl; “R” means lower alkyl unlessotherwise defined; “Ac” means acetyl; “py” means pyridine; “TES” meanstriethylsilyl; “TMS” means trimethyl-silyl; “TBS” means Me₂t-BuSi-; “Tf”means —SO₂CF₃; “BMDA” means BrMgNiPr₂; “Swern” means (COCl)₂, Et₃N;“LTMP” means lithium tetramethylpiperidide; “MOP” means2-methoxy-2-propyl; “BOM” means benzyloxymethyl; “LDA” means lithiumdiisopropylamide; “LAH” means lithium aluminum hydride; “Red-Al” meanssodium bis(2-methoxyethoxy) aluminum hydride; “Ms” means CH₃SO₂—; “TASF”means tris(diethylamino)-sulfonium-difluorotrimethylsilicate; “Ts” meanstoluene-sulfonyl; “TBAF” means tetrabutyl ammonium hydride; “TPAP” meanstetrapropyl-ammonium perruthenate; “DBU” means diazabicycloundecane;“DMAP” means p-dimethylamino pyridine; “LHMDS” means lithiumhexamethyldisilazide; “DMF” means dimethylformamide; “AIBN” meansazo-(bis)-isobutyronitrile; “10-DAB” means 10-desacetylbaccatin III;“FAR” means 2-chloro-1,1,2-trifluorotriethylamine; “mCPBA” meansmeta-chloroperbenzoic acid; “DDQ” means dicyanodichloroquinone;“sulfhydryl protecting group” includes, but is not limited to,hemithioacetals such as 1-ethoxyethyl and methoxymethyl, thioesters, orthiocarbonates; “amine protecting group” includes, but is not limitedto, carbamates, for example, 2,2,2-trichloroethylcarbamate ortertbutylcarbamate; “protected hydroxy” means —OP wherein P is a hydroxyprotecting group; and “hydroxy protecting group” includes, but is notlimited to, acetals having two to ten carbons, ketals having two to tencarbons, ethers such as methyl, t-butyl, benzyl, p-methoxybenzyl,p-nitrobenzyl, allyl, trityl, methoxymethyl, methoxyethoxymethyl,ethoxyethyl, tetrahydropyranyl, tetrahydrothiopyranyl, and trialkylsilylethers such as trimethylsilyl ether, triethylsilyl ether,dimethylarylsilyl ether, triisopropylsilyl ether andt-butyldimethylsilyl ether; esters such as benzoyl, acetyl,phenylacetyl, formyl, mono-, di-, and trihaloacetyl such aschloroacetyl, dichloroacetyl, trichloroacetyl, trifluoro-acetyl; andcarbonates including but not limited to alkyl carbonates having from oneto six carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl,t-butyl; isobutyl, and n-pentyl; alkyl carbonates having from one to sixcarbon atoms and substituted with one or more halogen atoms such as2,2,2-trichloroethoxymethyl and 2,2,2-tri-chloroethyl; alkenylcarbonates having from two to six carbon atoms such as vinyl and allyl;cycloalkyl carbonates having from three to six carbon atoms such ascyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; and phenyl orbenzyl carbonates optionally substituted on the ring with one or moreC₁₋₆ alkoxy, or nitro. Other hydroxyl, sulfhydryl and amine protectinggroups may be found in “Protective Groups in Organic Synthesis” by T. W.Greene, John Wiley and Sons, 1981.

[0092] The “hydrocarbon” moities described herein are organic compoundsor radicals consisting exclusively of the elements carbon and hydrogen.These moieties include alkyl, alkenyl, alkynyl, and aryl moieties. Thesemoieties also include alkyl, alkenyl, alkynyl, and aryl moietiessubstituted with other aliphatic or cyclic hydrocarbon groups, such asalkaryl, alkenaryl and alkynaryl. Preferably, these moieties comprise 1to 20 carbon atoms.

[0093] The alkyl groups described herein are preferably lower alkylcontaining from one to six carbon atoms in the principal chain and up to20 carbon atoms. They may be straight or branched chain and includemethyl, ethyl, propyl, isopropyl, butyl, hexyl and the like. They may besubstituted with aliphatic or cyclic hydrocarbon radicals orhetero-substituted with the various substituents defined herein.

[0094] The alkenyl groups described herein are preferably lower alkenylcontaining from two to six carbon atoms in the principal chain and up to20 carbon atoms. They may be straight or branched chain and includeethenyl, propenyl, isopropenyl, butenyl, isobutenyl, hexenyl, and thelike. They may be substituted with aliphatic or cyclic hydrocarbonradicals or hetero-substituted with the various substituents definedherein.

[0095] The alkynyl groups described herein are preferably lower alkynylcontaining from two to six carbon atoms in the principal chain and up to20 carbon atoms. They may be straight or branched chain and includeethynyl, propynyl, butynyl, isobutynyl, hexynyl, and the like. They maybe substituted with aliphatic or cyclic hydrocarbon radicals orhetero-substituted with the various substituents defined herein.

[0096] The aryl moieties described herein contain from 6 to 20 carbonatoms and include phenyl. They may be hydro-carbon or heterosubstitutedwith the various substituents defined herein. Phenyl is the morepreferred aryl.

[0097] The heteroaryl moieties described are heterocyclic compounds orradicals which are analogous to aromatic compounds or radicals and whichcontain a total of 5 to 20 atoms, usually 5 or 6 ring atoms, and atleast one atom other than carbon, such as furyl, thienyl, pyridyl andthe like. The heteroaryl moieties may be substituted with hydrocarbon,heterosubstituted hydrocarbon or hetero-atom containing substituentswith the hetero-atoms being selected from the group consisting ofnitrogen, oxygen, silicon, phosphorous, boron, sulfur, and halogens.These substituents include lower alkoxy such as methoxy, ethoxy, butoxy;halogen such as chloro or fluoro; ethers; acetals; ketals; esters;heteroaryl such as furyl or thienyl; alkanoxy; hydroxy; protectedhydroxy; acyl; acyloxy; nitro; amino; and amido.

[0098] The heterosubstituted hydrocarbon moieties described herein arehydrocarbon moieties which are substituted with at least one atom otherthan carbon, including moieties in which a carbon chain atom issubstituted with a hetero atom such as nitrogen, oxygen, silicon,phosphorous, boron, sulfur, or a halogen atom. These substituentsinclude lower alkoxy such as methoxy, ethoxy, butoxy; halogen such aschloro or fluoro; ethers; acetals; ketals; esters; heteroaryl such asfuryl or thienyl; alkanoxy; hydroxy; protected hydroxy; acyl; acyloxy;nitro; amino; and amido.

[0099] The acyl moieties described herein contain hydrocarbon,substituted hydrocarbon or heteroaryl moieties.

[0100] The alkoxycarbonyloxy moieties described herein comprise lowerhydrocarbon or substituted hydrocarbon moieties.

[0101] The following examples illustrate the invention.

EXAMPLE REACTION SCHEME 1

[0102] Hydroxyketone 2. To a stirred solution of 3,10-diol 1 (3.49 g,14.78 mmol) in 35 mL of DMF under nitrogen at 0° C. was added pyridiniumdichromate (“PDC”) (7.20 g, 19.15 mmol) as a solid in three portionsover a 30 min. period. The reaction mixture was then warmed to roomtemperature. After 6 h, the reaction mixture was poured into 500 mL ofH₂O and extracted with three 200 mL portions of 15% ethyl acetate inhexane. The organic layers were combined and dried over anhydrousNa₂SO₄. Removal of the solvent followed by flash chromatographypurification (10% EtOAc/hexane) gave 3.34 g (97% yield) of the desiredhydroxyketone 2 as a white solid.

[0103] 2: mp: 73-74° C.; ¹H NMR (300 MHz, CDCl₃) δ (ppm) 0.96 (s, 3H,Me16), 1.06 (s, 3H, Me17), 1.20 (d, J=7.1 Hz, 3H, Me19), 1.38 (d, J=14.8Hz, 1H, H2α), 1.70 (d, J=1.7 Hz, 3H, Me18), 1.76 (t, J=6.0 Hz, 1H, H1),2.00 (br d, J=18.1 Hz, 1H, H14α), 2.07 (dd, J=19.2, 7.7 Hz, 1H, H9β),2.45 (br d, J=18.1 Hz, 1H, H14β), 2.61 (ddq, J=11.5, 7.7, 7.1 Hz, 1H,H8α), 2.66 (dd, J=14.8, 6.0 Hz, 1H, H2β), 2.72 (dd, J=19.2, 11.5 Hz,1H9α), 2.81 (s, 1H, OH3), 5.43 (m, 1H, H13); ¹³C NMR (75 MHz, CDCl₃) δ(ppm) 16.40, 21.44, 21.75, 25.46, 33.48, 38.29, 44.68, 44.77, 47.06,48.41, 73.07, 94.19, 121.72, 138.34, 217.54; IR (CCl₄) υ 3520, 3000,2960, 2900, 2820, 1730, 1440, 1330, 990, 970 cm⁻¹; MS (CI) 235 (M⁺+1,100) 217 (65).

[0104] Triethylsilyl enol ether 3. To a stirred 0.94 M solution of LDAin THF (1.41 mL, 1.33 mmol) under nitrogen at −78° C. was added asolution of hydroxyketone 2 (156 mg, 0.667 mmol) in 1.5 mL of THF and0.23 mL of HMPA (1.33 mmol) dropwise down the side of the flask. After0.5 h, a 0.1 M solution (6.67 mL, 0.667 mmol) of TESCl in THF was addeddown the side of the flask at a rate of 0.1 mL/min. After the additionwas complete, the reaction mixture was stirred for an additional 5 min.and then rapidly poured into 50 mL of a vigorously stirred saturatedaqueous NaHCO₃ solution. The mixture was extracted with three 50 mLportions of hexane and the combined organic layers were washed with 20mL of H₂O, dried over anhydrous Na₂SO₄. Removal of the solvent followedby flash chromatography purification (10% EtOAc/hexane) gave 225 mg oftriethylsilyl enol ether 3 (97% yield) as a colorless oil.

[0105] 3: ¹H NMR (300 MHz, CDCl₃) δ (ppm) 0.71 (q, J=7.7 Hz, 6H, TESCH₂), 0.89 (s, 3H, Me16), 0.98 (t, J=7.7 Hz, 9H, TES CH₃), 1.06 (d,J=7.1 Hz, 3H, Me19), 1.13 (s, 3H, Me17), 1.28 (d, J=14.3 Hz, 1H, H2α),1.66 (dd, J=6.0, 5.5 Hz, 1H, H1), 1.76 (dd, J=2.2, 1.7 Hz, 3H, Me18),1.95 (br d, J=18.7 Hz, 1H, H14α), 2.33 (ddd, J=14.3, 6.0, 2.2 Hz, 1H,H2β), 2.42 (br d, J=18.7 Hz, 1H, H14β), 2.72 (qd, J=7.7, 2.1 Hz, 1H,H8α), 3.08 (s, 1H, OH3), 4.45 (d, J=2.1 Hz, 1H, H9), 5.50 (m, 1H, H13);¹³C NMR (75 MHz, CDCl₃) δ (ppm) 4.51, 6.46, 16.10, 21.58, 22.76, 25.10,33.57, 43.78, 44.11, 45.13, 45.16, 71.32, 91.75, 106.27, 120.82, 140.25,151.77; IR (CCl₄) υ 3510, 3010, 2960, 2910, 2880, 2830, 1630, 1440,1330, 1310, 1230, 1150, 1040, 1010, 880, 700 cm⁻¹; MS (CI) 349 (M⁺+1,54), 331 (100).

[0106] Triethylsilyloxy ketone 4. To a stirred solution of triethylsilylenol ether 3 (5.335 g, 15.33 mmol) in 300 mL of hexane under nitrogen at0° C. was added 6.427 g of NaHCO₃ (76.55 mmol) and 4.533 g ofm-chloroperoxybenzoic acid (67% purity, 17.60 mmol) in four portionsover a 0.5 h period. After 2.5 h, the reaction mixture was diluted with200 mL of hexane and poured into 400 mL of a 1:1 mixture of a saturatedaqueous NaHCO₃ solution and a saturated aqueous Na₂S₂O₃ solution. Theorganic layer was separated, and the aqueous layer was extracted withtwo 100 mL portions of hexane. The combined organic layers were washedwith 100 mL of H₂O, dried over anhydrous Na₂SO₄, and concentrated underreduced pressure to give 5.7 g of a yellowish oil. This material waspurified by flash chromatography (5% EtOAc/hexane) to give 5.495 g oftriethylsilyloxy ketone 4 (98% yield) as a colorless oil.

[0107] 4: ¹H NMR (300 MHz, CDCl₃) δ (ppm) 0.65 (q, J=7.7 Hz, 6H, TESCH₂), 0.90 (s, 3H, Me16), 0.97 (t, J=7.7 Hz, 9H, TES CH₃), 1.06 (s, 3H,Me17), 1.11 (d, J=7.7 Hz, 3H, Me19), 1.39 (d, J=14.8 Hz, 1H, H2α), 1.76(d, J=1.7 Hz, 3H, Me18), 1.76 (dd, J=6.1, 5.5 Hz, 1H, H1), 2.17 (br d,J=18.7 Hz, 1H, H14α), 2.33 (dq, J=9.3, 7.7 Hz, 1H, H8α), 2.46 (br d,J=18.7 Hz, 1H, H14β), 2.64 (ddd, J=14.8, 6.1, 2.2 Hz, 1H, H2β), 2.79 (brs, 1H, OH3), 3.85 (d, J=9.3 Hz, 1H, H9), 5.54 (m, 1H, H13); ¹³C NMR (75MHz, CDCl₃) δ (ppm) 4.90, 6.48, 13.98, 21.47, 21.94 26.94, 33.42, 44.33,44.49, 46.79, 48.59, 70.51, 83.33, 90.04, 121.71, 138.66, 214.42; IR(CCl₄) υ 3520, 3000, 2960, 2920, 2880, 2830, 1730, 1450, 1330, 1220,1160, 1105, 980, 960, 920, 700 cm⁻¹; MS (CI) 365 (M⁺+1, 34), 347 (100),335 (42), 233 (35).

[0108] Triethylsilyloxy diol 5. To a stirred suspension of 0.263 g(6.932 mmol) of lithium aluminum hydride in 30 mL of ethyl ether undernitrogen at 0° C. was added a solution of 2.527 g (6.932 mmol) oftriethylsilyloxy ketone 4 in 20 mL of ethyl ether. The reaction mixturewas warmed to room temperature. After 2 h at room temperature, themixture was recooled to 0° C., diluted with 50 mL of ethyl ether, andquenched by dropwise addition of 2.5 mL of H₂O. After stirring another 2h at room temperature, the white suspension was further diluted with 100mL of ethyl acetate, dried over anhydrous Na₂SO₄, and filtered through a0.5 inch pad of celite. The filtrate was concentrated under reducedpressure to give 2.434 g of triethylsilyloxy diol 5 (96% yield) as awhite solid, which was used without any further purification.

[0109] 5: mp: 62-63° C.; ¹H NMR (300 MHz, CDCl₃) δ (ppm) 0.62 (q, J=7.7Hz, 6H, TES CH₂), 0.97 (t, J=7.7 Hz, 9H, TES CH₃), 1.08 (s, 3H, Me16),1.09 (d, J=7.1 Hz, 3H, Me19), 1.18 (d, J=14.8 Hz, 1H, H2α), 1.20 (s, 3H,Me17), 1.48 (dd, J=6.6, 6.1 Hz, 1H, H1), 1.84 (d, J=1.7 Hz, 3H, Me18),1.97 (dq, J=8.8, 7.1 Hz, 1H, H8α), 2.17 (br d, J=18.7 Hz, 1H, H14α),2.43 (br d, J=18.7 Hz, 1H, H14β), 2.47 (ddd, J=14.8, 6.1, 2.2 Hz, 1H,H2β), 2.74 (br s, 1H, OH3), 4.01 (dd, J=8.8, 8.2 Hz, 1H, H9β), 4.28 (d,J=8.2 Hz, 1H, H10), 5.55 (m, 1H, H13); ¹³C NMR (75 MHz, CDCl₃) δ (ppm)5.16, 6.60, 12.82, 21.96, 23.63, 27.76, 33.88, 44.16, 44.96, 45.31,48.27, 63.33, 81.46, 83.37, 122.03, 141.62; IR (CCl₄) υ 3640, 3550,3020, 2970, 2920, 2890, 2850, 1450, 1330, 1240, 1160, 1140, 1120, 1100,1080, 1040, 1000, 970, 960, 860, 840, 710 cm⁻¹; MS (CI) 367 (M⁺+1, 21),349 (100), 337 (22), 319 (42).

[0110] Triethylsilyloxy keto diol 6. To a vigorously stirred solution oftriethylsilyloxy diol 5 (886 mg, 2.42 mmol) in 25 mL of CH₂Cl₂ at 0° C.under nitrogen was added 1.08 mL (3.63 mmol) of Ti(Oi-Pr)₄ followed bydropwise addition of 1.82 mL (3.63 mmol) of a 2 M solution of t-BuOOH inhexane. After an additional 2 h, 2.5 mL of dimethyl-sulfide was addedand the reaction mixture was warmed in a 42° C. bath to reflux for 12 h.The solvent was evaporated under reduced pressure. The residue wasdissolved in 200 mL of THF at room temperature and 0.5 mL of H₂O wasadded dropwise with vigorously stirring. After 2 h, the resulting whitesuspension was dried over anhydrous Na₂SO₄, and then filtered through a0.5 inch pad of celite, eluting with two 50 mL portions of ethylacetate. The filtrate was concentrated under reduced pressure to afforda yellow oil. This oil was purified by flash chromatography (10%EtOAc/hexane) to give 866.7 mg of triethylsilyloxy keto diol 6 (94%yield) as a white solid.

[0111] 6: mp 106-107° C.; ¹H NMR (300 MHz, CDCl₃) δ (ppm) 0.71 (q, J=7.7Hz, 6H, TES CH₂), 1.01 (t, J=7.7 Hz, 9H, TES CH₃), 1.01 (s, 3H, Me17),1.07 (d, J=7.1 Hz, 3H, Me19), 1.53 (s, 3H, Me16), 1.73 (s, 3H, Me18),1.80-1.94 (m, 3H, H1, H2β, H14α), 2.02 (d, J=3.3 Hz, 1H, OH10), 2.22(dq, J=9.9, 7.1 Hz, 1H, H8α), 2.52 (d, J=12.1 Hz, 1H, OH13), 2.81 (dd,J=11.5, 3.3 Hz, 1H, H2α) 2.83 (m, 1H, H14β), 4.08 (br t, J=11.5 Hz, 1H,H13), 4.16 (dd, J=9.9, 8.8 Hz, 1H, H9), 4.56 (dd, J=8.8, 3.3 Hz, 1H,H10); ¹³C NMR (75 MHz, CDCl₃) δ (ppm) 5.36, 6.72, 15.84, 17.96, 26.11,29.30 34.83, 38.44, 41.00, 45.98, 54.49, 66.94, 77.15, 77.21, 137.66,140.65, 215.86; IR (CCl₄) υ 3650, 3550, 3460, 2980, 2900, 2870, 1670,1455, 1410, 1370, 1280, 1240, 1210, 1160, 1090, 1050, 1030, 1010, 960,860, 720 cm⁻¹; MS (EI) 382 (M⁺, 2), 353 (10), 335 (5), 307 (4), 250 (4),215 (67), 75 (100).

[0112] t-Butyldimethylsilyloxy ketone 7. To a stirred solution oftriethylsilyloxy keto diol 6 (883 mg, 2.31 mmol) in 35 mL of pyridineunder nitrogen at 0° C. was added dropwise 0.485 mL (2.771 mmol) ofTBSOTf. The solution was then warmed to room temperature. After 2 h atroom temperature, the solution was diluted with 100 mL of hexane andpoured into 150 mL of a saturated aqueous NaHCO₃ solution. The organiclayer was separated, and the aqueous layer was extracted with two 100 mLportions of hexane. The organic layers were combined, and washed with 50mL of a 10% aqueous CuSO₄ solution followed by 20 mL of H₂O, and driedover anhydrous Na₂SO₄. Removal of the solvent followed by flashchromatography purification (2.5% EtOAc/hexane) to give 1.122 g oft-butyldimethylsilyloxy ketone 7 (98% yield) as a white solid.

[0113] 7: mp: 128-130° C.; ¹H NMR (300 MHz, CDCl₃) δ (ppm) 0.04 (s, 3H,TBS CH₃), 0.06 (s, 3H, TBS CH₃), 0.63 q, J=7.7 Hz, 6H, TES CH₂), 0.93(s, 9H, TBS t-Bu), 1.01 (t, J=7.7 Hz, 9H, TES CH₃), 1.06 (d, J=7.1 Hz,3H, Me19), 1.09 (s, 3H, Me17), 1.56 (s, 3H, Me16), 1.66 (d, J=1.1 Hz,3H, Me18), 1.82 (m, 1H, H1), 1.85 (m, 1H, H2β), 1.90 (d, J=3.3 Hz, 1H,OH10), 1.93 (dd, J=14.3, 5.5 Hz, 1H, H14α), 2.16 (dq, J=10.4, 7.1 Hz,1H, H8α), 2.49 (ddd, J=14.3, 7.8, 2.2 Hz, 1H, H14β), 2.72 (dd, J=12.1,2.7 Hz, 1H, H2α), 4.19 (dd, J=10.4, 8.8 Hz, 1H, H9), 4.46 (ddd, J=7.8,5.5, 1.1, 1H, H13), 4.58 (dd, J=8.8, 3.3 Hz, 1H, H10); ¹³C NMR (75 MHz,CDCl₃) υ (ppm) −5.48, −4.54, 5.33, 6.68, 15.30, 16.42, 17.77, 25.65,27.15, 27.38, 33.93 38.94, 41.26, 45.83, 53.87, 67.27, 77.23, 77.61,135.08, 142.06, 209.77; IR (CCl₄) υ 3530, 2950, 2930, 2870, 1670, 1460,1250, 1090, 1030, 1010, 970, 910, 870, 830, 770, 740 cm⁻¹; MS (CI) 497(M⁺+1, 16), 479 (100), 365 (28), 346 (35), 307 (22), 205 (91).

[0114] Trimethylsilyl enol ether 8. To a stirred solution oft-butyldimethylsilyloxy ketone 7 (287 mg, 0.55 mmol) in 2.5 mL of THFand 0.3 mL of HMPA (3.3 mmol) under nitrogen at room temperature, wasadded dropwise a solution of 0.44 M LDA in THF (3.8 mL, 1.65 mmol).After stirring at room temperature for 10 min., a 1.0 M solution ofTMSCl (1.7 mL, 1.65 mmol) in THF was added dropwise at a rate of 0.1mL/min. After the addition was complete, the reaction was stirred foranother 2 minutes. Then 2.5 mL of triethylamine was added and thereaction mixture was poured into 150 mL of a saturated aqueous NaHCO₃solution. The aqueous layer was extracted with three 50 mL portions ofhexane. The combined organic layers were washed with 50 mL of H₂O, driedover anhydrous Na₂SO₄ and concentrated under reduced pressure to give370 mg of trimethylsilyl enol ether 8 (99% yield) as a colorless oil.This material was used in the next step without further purification.

[0115] 8: ¹H NMR (500 MHz, CDCl₃) δ (ppm) 0.08 (s, 3H, TBS CH₃), 0.11(s, 3H, TBS CH₃), 0.14 (s, 9H, TMS CH₃), 0.16 (s, 9H, enol TMS CH₃),0.63 (q, J=7.5 Hz, 6H, TES CH₂), 0.81 (d, J=7.0 Hz, 3H, Me19), 0.92 (s,9H, TBS t-Bu), 0.98 (t, J=7.5 Hz, 9H, TES CH₃), 1.09 (s, 3H, Me17), 1.23(ddd, J=14.0, 10.5, 5.5 Hz, 1H, H14α), 1.24 (s, 3H, Me16), 1.81 (d,J=1.5 Hz, 3H, Me18), 1.96 (ddd, J=10.5, 8.5, 5.5 Hz, 1H, H1), 2.30 (dq,J=7.0, 7.0 Hz, 1H, H8α), 2.51 (ddd, J=14.0, 10.5, 7.5 Hz, 1H, H14β),3.77 (dd, J=7.0, 6.4 Hz, 1H, H9), 4.63 (d, J=6.4 Hz, 1H, H10), 4.67(ddd, J=10.5, 7.5, 1.5 Hz, 1H, H13), 4.95 (d, J=8.5 Hz, 1H, H2); ¹³C NMR(75 MHz, CDCl₃) δ (ppm) −5.27, −4.71, 1.06, 0.53, 4.96, 6.86, 12.94,15.72, 18.11, 25.77, 28.76, 32.02, 37.54, 40.70, 41.79, 41.90, 69.53,78.61, 80.96, 112.22, 139.48, 139.87, 155.26; IR (CHCl₃) υ 2960, 2880,2870, 1680, 1630, 1460, 1250, 1130, 1080, 1000, 900, 880, 830 cm⁻¹; MS(CI) 641 (M⁺+1, 9), 551 (65), 508 (100), 379 (80).

[0116] Hydroxy ketone 9. To a stirred solution of 321 mg (0.501 mmol) oftrimethylsilyl enol ether 8 in 15 mL of THF under nitrogen at 0° C. wasadded 216 mg (80% pure, 1.00 mmol) of m-chloroperoxybenzoic acid as asolid in three portions. After 3 h, the reaction mixture was dilutedwith 50 mL of hexane and poured into 200 mL of a 1:1 mixture of asaturated aqueous NaHCO₃ solution and a saturated aqueous Na₂S₂O₃solution. The organic layer was separated, and the aqueous layer wasextracted with three 100 mL portions of hexane. The combined organiclayers were washed with 100 mL of H₂O, dried over anhydrous Na₂SO₄, andconcentrated under reduced pressure to give 332 mg of the correspondingtrimethyl-silyloxy epoxide as a white solid. This material was used inthe next step without further purification.

[0117] A solution of 332 mg of the above trimethylsilyloxy epoxide (ca.0.501 mmol) in 5 mL of methanol and 0.5 mL of CHCl₃ was stirred at roomtemperature for 24 h. Removal of the solvent followed by flashchromatography purification (5% EtOAc/hexane) gave 266 mg of hydroxyketone 9 as a white solid (91% yield from trimethylsilyl enol ether 8).

[0118] 9: mp: 111-112° C.; ¹H NMR (300 MHz, CDCl₃) δ (ppm) 0.04 (s, 3H,TBS CH₃), 0.07 (s, 3H, TBS CH₃), 0.18 (s, 9H, TMS CH₃), 0.62 (q, J=7.7Hz, 6H, TES CH₂), 0.93 (s, 9H, TBS t-Bu), 0.97 (t, J=7.7 Hz, 9H, TESCH₃), 1.06 (d, J=7.1 Hz, 3H, Me19), 1.08 (s, 3H, Me17), 1.35 (s, 3H,Me16), 1.65 (s, 3H, Me18), 1.81 (dd, J=14.8, 4.4 Hz, 1H, H14α), 1.95(dd, J=7.7, 3.8 Hz, 1H, H1), 2.26 (ddd, J=14.8, 10.4, 7.7 Hz, 1H, H14β),2.30 (dq, J=10.4, 7.1 Hz, 1H, H8α), 3.30 (d, J=8.3 Hz, 1H, OH2), 4.22(dd, J=10.4, 8.8 Hz, 1H, H9), 4.35 (br dd, J=10.4, 4.4 Hz, 1H, H13),4.41 (dd, J=8.3, 3.8 Hz, 1H, H2), 4.54 (d, J=8.8 Hz, 1H, H10); ¹³C NMR(75 MHz, CDCl₃) δ (ppm) −5.44, −4.52, 0.95, 4.85, 6.81, 15.46, 17.62,17.83, 25.65, 26.22, 28.21, 28.39, 36.69, 52.19, 54.33, 66.94, 71.25,75.74, 77.43, 137.10, 140.25, 211.59; IR (CCl₄) υ 3530, 2960, 2890,2870, 1680, 1460, 1240, 1160, 1120, 1080, 1060, 1020, 1000, 990, 880,830 cm⁻¹; MS (CI) 585 (M⁺+1, 34), 584 (69), 567 (13), 453 (100), 363(30), 323 (52).

[0119] Triol 10. To a solution of 4-bromo-4-penten-1-ol (770.0 mg, 4.7mmol) in 20 mL of Et₂O at −78° C. under N₂ was added a 1.7 M solution oft-BuLi (8 mL, 13.6 mmol) in hexane. The solution was then stirred at 0°C. for 2 h. After cooling to −10° C., a solution of hydroxy ketone 9(370 mg, 0.63 mmol) in 5 mL of Et₂O was added. The solution was stirredat —10° C. for 0.5 h, and then poured into 150 mL of a saturated aqueousNaHCO₃ solution. The aqueous layer was extracted with EtOAc (100 mL, 3times). The combined organic layers were dried over Na₂SO₄, and thesolvent was removed under reduced pressure. The residue was purified byflash chromatography (20% EtOAc/hexane) to give 400 mg (95% yield) ofthe desired triol 10 as a colorless oil.

[0120] 10: ¹H NMR (500 MHz, CDCl₃): δ (ppm) 0.136 (s, 12H, TMS CH₃, TBSCH₃), 0.159 (s, 3H, TBS CH₃), 0.669 (qd, J=8.0, 1.5 Hz, 6H, TES CH₂),0.770 (d, J=7.0 Hz, 3H, Me19), 0.921 (s, 9H, TBS t-Bu), 0.991 (t, J=8.0Hz, 9H, TES CH₃), 1.038 (s, 3H, Me17), 1.488 (s, 3H, Me16), 1.702 (t,J=6.0 Hz, 1H, OH7), 1.729 (s, 3H, Me18), 1.779-1.830 (m, 3H, 2×H6, H8),1.869 (dd, J=9.0, 2.8 Hz, 1H, H1), 2.101 (m, 2H, 2×H5), 2.134 (d, J=16.0Hz, 1H, H14α), 2.545 (dt, J=16.0, 9.0 Hz, 1H, H14β), 2.905 (br, 1H,OH2), 3.473 (s, 1H, OH3), 3.670-3.726 (m, 2H, 2×H7), 4.060 (m, 1H, H2β),4.070 (dd, J=8.0, 6.5 Hz, 1H, H9β), 4.250 (d, J=8.0 Hz, 1H, H10α), 4.322(d, J=9.0 Hz, 1H, H13β), 4.968 (s, 1H, 1×H20), 5.190 (s, 1H, 1×H20); ¹³CNMR (75 MHz, CDCl₃): δ (ppm) −5.19, −4.57, 0.89, 5.05, 6.83, 13.10,17.74, 19.33, 25.54, 26.18, 28.64, 29.94, 30.97, 34.40, 35.78, 45.27,51.44, 62.31, 68.88, 73.80, 79.87, 83.83, 109.95, 135.03, 142.32; IR(CHCl₃): υ 2950, 2870, 1090, 1060, 980, 890 cm⁻¹; MS (CI): 653(M⁺+1-H₂O), 539, 521, 503, 449, 431, 407, 390, 316, 294, 244.

[0121] Carbonate 11. To a solution of triol 10 (405 mg, 0.60 mmol) in 20mL of CH₂Cl₂ at −78° C. under N₂ was added 4.7 mL (60.0 mmol) ofpyridine, followed by a solution of COCl₂ (6.0 mL, 6.0 mmol) in toluene.The mixture was then warmed to 0° C. and stirred at that temperature for50 minutes. Then the mixture was diluted with 100 mL of EtOAc and pouredinto 200 mL of a saturated aqueous NaHCO₃ solution. The organic layerwas separated, and aqueous layer was extracted with EtOAc (100 mL, 3times). The organic layers were combined and dried over Na₂SO₄. Removalof the solvent gave the desired carbonate 11 a pale yellow oil, whichwas used without further purification.

[0122] 11: ¹H NMR (500 MHz, CDCl₃): δ (ppm) 0.085 (s, 3H, TBS CH₃),0.100 (s, 12H, TBS CH₃, TMS CH₃), 0.652 (qd, J=7.5, 1.5 Hz, 6H, TESCH₂), 0.912 (s, 9H, TBS t-Bu), 0.950 (d, J=6.0 Hz, 3H, Me19), 0.984 (t,J=7.5 Hz, 9H, TES CH₃), 1.199 (s, 3H, Me17), 1.434 (ddd, J=18.5, 9.0,4.5 Hz, 1H, H14α), 1.481 (s, 3H, Me16), 1.637 (m, 1H, 1×H6), 1.722 (m,1H, 1×H6), 1.786 (d, J=1.0 Hz, 3H, Me18), 2.192-2.349 (m, 4H, 2×H5, H1,H14β), 2.396 (qd, J=6.0, 5.0 Hz, 1H, H8), 3.658 (qd, J=6.5, 3.0 Hz, 2H,2×H7), 3.982 (dd, J=8.0, 5.0 Hz, 1H, H9β), 4.509 (d, J=8.0 Hz, 1H,H10α), 4.771 (td, J=9.0, 1.0 Hz, 1H, H13β), 4.858 (d, J=4.0 Hz, 1H, H2),5.275 (s, 2H, 2×H20).

[0123] Acetate 12. To a solution of the above carbonate 11 in 5 mL ofpyridine at room temperature under N₂ was added Ac₂O (0.6 mL, 6.3 mmol).After stirring at room temperature for 9 h, the solution was dilutedwith 100 mL of 20% EtOAc in hexane, and poured into 100 mL of asaturated aqueous NaHCO₃ solution. The organic layer was separated, andthe aqueous layer was extracted with 20% EtOAc in hexane (100 mL, 3times). The organic layers were combined and dried over Na₂SO₄. Removalof the solvent followed by flash chromatography purification (8%EtOAc/hexane) gave 433.2 mg (98% yield) of the desired acetate 12 as acolorless oil.

[0124] 12: ¹H NMR (500 MHz, CDCl₃): δ (ppm) 0.085 (s, 3H, TBS CH₃),0.097 (s, 12H, TMS CH₃, TBS CH₃), 0.654 (qd, J=8.0, 2.0 Hz, 6H, TESCH₂), 0.913 (s, 9H, TBS t-Bu), 0.935 (d, J=7.5 Hz, 3H, Me19), 0.985 (t,J=8.0 Hz, 9H, TES CH₃), 1.201 (s, 3H, Me17), 1.429 (m, 1H, H14α), 1.480(s, 3H, Me16), 1.711 (m, 1H, 1×H6), 1.788 (s, 3H, Me18), 1.820 (m, 1H,1×H6), 2.041 (s, 3H, COCH₃), 2.153-2.351 (m, 4H, H1, 2×H5, H14β), 2.403(dq, J=8.0, 7.5 Hz, 1H, H8), 3.977 (dd, J=8.0, 5.5 Hz, 1H, H9β), 4.075(t, J=6.5 Hz, 2H, 2×H7), 4.510 (d, J=8.0 Hz, 1H, H10α), 4.771 (t, J=8.0Hz, 1H, H13β), 4.835 (d, J=4.0 Hz, 1H, H2β), 5.253 (s, 1H, 1×H20), 5.286(s, 1H, 1×H20); ¹³C NMR (75 MHz, CDCl₃): δ (ppm) −5.37, −4.74, 0.79,4.98, 6.74, 12.93, 15.61, 17.92, 20.53, 25.63, 27.36, 28.27, 29.77,32.34, 32.98, 36.48, 39.11, 48.96, 63.55, 68.84, 73.02, 79.66, 88.61,92.86, 114.68, 137.48, 141.39, 150.56, 154.08, 171.14; IR (CHCl₃): υ2950, 2850, 1790, 1713, 1020, 880, 815 cm⁻¹; MS (CI): 739 (M⁺+1), 691,665, 607, 563, 503, 473, 431.

[0125] Hydroxy alkene 13. To a solution of acetate 12 (433.0 mg, 0.586mmol) in 2 mL of CH₃CN at 0° C. was added 5.0 mL of a solution of 48%HF/pyridine/CH₃CN (1:8:8). After stirring at 0° C. for 3 h, the solutionwas diluted with 50 mL of EtOAc and poured into 100 mL of a saturatedaqueous NaHCO₃ solution. The organic layer was separated, and theaqueous layer was extracted with EtOAc (100 mL, 3 times). The organiclayers were combined and dried over Na₂SO₄. Removal of the solvent gavea pale yellow oil, which was used without further purification To asolution of the above oil in 4 mL of CH₂Cl₂ at room temperature under N₂was added Et₃N (0.32 mL, 2.3 mmol), followed by TESCl (0.20 mL, 1.2mmol). After stirring at room temperature for 1.5 h, the solution wasdiluted with 100 mL of 20% EtOAc in hexane, and poured into 100 mL of asaturated aqueous NaHCO₃ solution. The organic layer was separated, andthe aqueous layer was extracted with 20% EtOAc in hexane (100 mL, 3times). The organic layers were combined and dried over Na₂SO₄. Removalof the solvent followed by flash chromatography purification (15% EtOAc/hexane) gave 351.0 mg of the desired hydroxy alkene 13 (90% yield) as acolorless oil, plus 2.3% starting material 12 and 1.1% 9,10-diol.

[0126] 13: ¹H NMR (500 MHz, CDCl₃): δ (ppm) 0.090 (s, 3H, TBS CH₃),0.104 (s, 3H, TBS CH₃), 0.662 (qd, J=8.0, 1.5 Hz, 6H, TES CH₂), 0.915(s, 9H, TBS t-Bu), 0.965 (d, J=7.5 Hz, 3H, Me19), 0.989 (t, J=8.0 Hz,9H, TES CH₃), 1.197 (s, 3H, Me17), 1.486 (s, 3H, Me16), 1.434 (dd,J=9.5, 4.7 Hz, 1H, H14α), 1.780 (m, 1H, 1×H6), 1.810 (d, J=1.5 Hz, 3H,Me18), 1.942 (m, 1H, 1×H6), 2.045 (s, 3H, COCH₃), 2.191 (m, 1H, 1×H5),2.208 (d, J=2.5 Hz, 1H, OH9), 2.262-2.333 (m, 3H, 1×H5, H1, H8), 2.360(m, 1H, H14β), 3.986 (m, 1H, H9β), 4.112 (td, J=6.5, 2.5 Hz, 2H, 2×H7),4.512 (d, J=8.5 Hz, 1H, H10α), 4.760-4.791 (m, 2H, H13β, H2), 5.201 (s,1H, 1×H20), 5.320 (s, 1H, 1×H20); ¹³C NMR (75 MHz, CDCl₃): δ (ppm)−5.41, −4.72, 4.64, 5.49, 11.23, 15.89, 17.88, 20.52, 25.60, 27.13,27.44, 28.09, 32.49, 33.16, 36.72, 36.83, 49.11, 63.52, 68.78, 70.99,79.13, 86.15, 92.71, 114.00, 136.37, 141.98, 147.57, 154.21, 171.20; IR(CHCl₃): υ 2960, 2780, 1795, 1735, 1000, 865 cm⁻¹; MS (CI): 667 (M⁺+1),649, 623, 605, 587, 535, 473.

[0127] Ketone 14. To a mixture of hydroxy alkene 13 (343.0 mg, 0.515mmol) and 200 mg of 3A° molecular sieves in 5 mL of CH₂Cl₂ at roomtemperature under N₂ was added 4-methyl-morpholine (180 mg, 1.54 mmol)followed by tetra-propylammonium perruthenate (18 mg, 0.05 mmol). Afterstirring at room temperature for 2 h, the mixture was filtered through ashort pad of silica gel. The silica gel was washed with 200 mL of 15%EtOAc in hexane. Removal of the solvent gave 338.5 mg of the desiredketone 14 (99% yield) as a colorless oil, which was used without anyfurther purification.

[0128] 14: ¹H NMR (500 MHz, CDCl₃): δ (ppm) 0.116 (s, 3H, TBS CH₃),0.132 (s, 3H, TBS CH₃), 0.635 (qd, J=7.5, 4.0 Hz, 6H, TES CH₂), 0.936(s, 9H, TBS t-Bu), 0.961 (t, J=7.5 Hz, 9H, TES CH₃), 1.051 (d, J=7.0 Hz,3H, Me19), 1.203 (s, 3H, Me17), 1.232 (s, 3H, Me16), 1.534 (m, 1H,H14α), 1.807 (m, 1H, 1×H6), 1.885-1.981 (m, 2H, 1×H5, 1×H6), 1.942 (d,J=1.5 Hz, 3H, Me18), 2.059 (s, 3H, COCH₃), 2.242 (ddd, J=15.5, 10.5, 4.0Hz, 1H, 1×H5), 2.333-2.418 (m, 2H, H14β, H1), 3.523 (q, J=7.0 Hz, 1H,H8), 4.103 (t, J=6.0 Hz, 2H, 2×H7), 4.773 (d, J=4.5 Hz, 1H, H2β), 4.868(m, 1H, H13β), 4.935 (s, 1H, H10α), 5.282 (s, 1H, 1×H20), 5.320 (s, 1H,1×H20); ¹³C NMR (75 MHz, CDCl₃): δ (ppm) −5.44, −4.78, 4.60, 6.34,15.11, 15.54, 17.91, 20.53, 25.60, 25.68, 27.01, 28.00, 32.35, 32.88,36.69, 42.40, 47.82, 63.46, 68.70, 79.56, 85.00, 90.58, 115.91, 134.62,143.46, 145.91, 153.47, 171.15, 209.74; IR (CHCl₃): υ 2960, 2880, 1800,1750, 1000, 865 cm⁻¹; MS (CI): 665 (M⁺+1), 648, 637, 621, 533, 489.

[0129] Hydroxy ketone 15. To a 0.1 M solution of Pd(acac)₂/n-Bu₃P (1:1)in DMF (1 mL, 0.1 mmol) at room temperature under N₂ was added a 2.37 Msolution of HCOOH/Et₃N (1:1) in DMF (10.2 mL, 24.2 mmol), followed by asolution of ketone 14 (320.0 mg, 0.48 mmol) in 5 mL of DMF. Afterstirring at room temperature for 19 h, the solution was diluted with 100mL of Et₂O and poured into 100 mL of a saturated aqueous NaHCO₃solution. The organic layer was separated, and the aqueous layer wasextracted with Et₂O (100 mL, 3 times). The organic layers were combinedand dried over Na₂SO₄. Removal of the solvent followed by flashchromatography purification (15% EtOAc/hexane) gave 280.5 mg (94% yield)of the desired hydroxy ketone 15 as a colorless oil.

[0130] 15: ¹H NMR (500 MHz, CDCl₃): δ (ppm) 0.138 (s, 3H, TBS CH₃),0.149 (s, 3H, TBS CH₃), 0.628 (qd, J=7.5, 3.0 Hz, 6H, TES CH₂), 0.892(d, J=7.0 Hz, 3H, Me19), 0.953 (s, 9H, TBS t-Bu), 0.962 (t, J=7.5 Hz,9H, TES CH₃), 1.104 (s, 3H, Me17), 1.201 (s, 3H, Me16), 1.409 (ddd,J=14.5, 4.5, 4.0 Hz, 1H, H14α), 1.464 (q, J=6.0 Hz, 1H, 1×H5), 1.783(br, 1H, OH2), 1.805-1.863 (m, 2H, 2×H6), 1.910 (d, J=1.0 Hz, 3H, Me18),2.054 (m, 1H, H1), 2.063 (s, 3H, COCH₃), 2.367-2.473 (m, 3H, H14β, 1×H5,H3), 3.024 (dq, J=9.0, 7.0 Hz, 1H, H8), 3.880 (ddd, J=9.5, 2.5, 2.0 Hz,1H, H2β), 4.102 (m, 1H, 1×H7), 4.154 (m, 1H, 1×H7), 4.790 (ddd, J=9.0,4.5, 1.0 Hz, 1H, H13β), 4.899 (s, 1H, H10α), 5.012 (s, 1H, 1×H20), 5.097(s, 1H, 1×H20).

[0131] Hydroxy ketone 16. To a solution of hydroxy ketone 15 (450.0 mg,0.72 mmol) in 15 mL of CH₂Cl₂ at room temperature under N₂ was addeddiisopropylethylamine (1.25 mL, 7.2 mmol), followed bytetrabutylammonium iodide (265.0 mg, 0.72 mmol), andbenzyloxymethylchloride (0.5 mL, 3.6 mmol). After stirring at roomtemperature for 24 h, another 1.25 mL (7.2 mmol) ofdiisopropylethylamine followed by 0.5 mL (3.6 mmol) ofbenzyloxymethylchloride was added. The solution was stirred at roomtemperature for another 24 h, and then was heated to 40° C. for 2 h.After being recooled to room temperature, the solution was diluted with50 mL of THF and 5 mL of MeOH. Then a 0.1 N aqueous solution of NaOH (10mL, 1.0 mmol) was added. After stirring at room temperature for 1.5 h,the solution was diluted with 100 mL of 20% EtOAc in hexane, and pouredinto 50 mL of a saturated aqueous NaHCO₃ solution. The organic layer wasseparated, and the aqueous layer was extracted with 20% EtOAc in hexane(50 mL, 3 times). The organic layers were combined, washed with 50 mL ofa saturated aqueous NH₄Cl solution, 50 mL of a saturated aqueous NaHCO₃solution, and then dried over Na₂SO₄. Removal of the solvent followed byflash chromatography purification (20% EtOAc/hexane) gave 430.0 mg (85%yield) of the desired hydroxy ketone 16 as a colorless oil.

[0132] 16: ¹H NMR (500 MHz, CDCl₃): δ (ppm) 0.140 (s, 3H, TBS CH₃),0.150 (s, 3H, TBS CH₃), 0.636 (qd, J=8.0, 4.0 Hz, 6H, TES CH₂), 0.939(d, J=7.0 Hz, 3H, Me19), 0.949 (t, J=8.0 Hz, 9H, TES CH₃), 0.967 (s, 9H,TBS t-Bu), 1.078 (s, 3H, Me17), 1.202 (s, 3H, Me16), 1.450 (ddd, J=15.0,8.5, 5.0 Hz, 1H, H14α), 1.661 (t, J=6.0 Hz, 1H, OH20), 1.695-1.821 (m,2H, 2×H6), 1.910 (d, J=1.0 Hz, 3H, Me18), 2.055 (m, 1H, 1×H5), 2.174 (m,1H, H1), 2.258 (m, 1H, 1×H5), 2.317 (m, 1H, H14β), 2.473 (dd, J=10.0,7.0 Hz, 1H, H3), 3.100 (dq, J=7.0, 7.0 Hz, 1H, H8α), 3.615-3.693 (m, 2H,2×H7), 3.967 (dd, J=10.0, 3.0 Hz, 1H, H2β), 4.548 (d, J=12.0 Hz, 1H,1H×BOM), 4.596 (d, J=12.0 Hz, 1H, 1H×BOM), 4.601 (d, J=7.0 Hz, 1H,1H×BOM), 4.710 (d, J=7.0 Hz, 1H, 1H×BOM), 4.836 (br td, J=8.5, 1.0 Hz,1H, H13β), 4.868 (s, 1H, H10α), 5.009 (br s, 1H, 1×H20), 5.014 (br s,1H, 1×H20), 7.277-7.346 (m, 5H, 5H×BOM); ¹³C NMR (75 MHz, CDCl₃): δ(ppm) −5.34, −4.69, 4.61, 6.48, 15.57, 17.88, 18.03, 25.74, 26.01,30.05, 32.40, 32.73, 36.60, 37.27, 47.32, 53.74, 62.22, 69.32, 69.69,79.84, 82.51, 94.65, 113.60, 127.57, 127.70, 128.52, 135.67, 138.25,141.04, 148.02, 215.16.

[0133] Keto aldehyde 17. To a mixture of hydroxy ketone 16 (130.0 mg,0.186 mmol) and 150 mg of 3A° molecular sieves in 5 mL of CH₂Cl₂ at roomtemperature under N₂ was added 4-methyl-morpholine (65.0 mg, 0.55 mmol)followed by tetrapropylammonium perruthenate (7.0 mg, 0.02 mmol). Afterstirring at room temperature for 2 min., the mixture was filteredthrough a short pad of silica gel. The silica gel was washed with 50 mLof 10% EtOAc in hexane. Removal of the solvent gave 116.8 mg (90% yield)of desired keto aldehyde 17 as a colorless oil, which was used withoutfurther purification.

[0134] 17. ¹H NMR (300 MHz, CDCl₃): δ (ppm) 0.128 (s, 3H, TBS CH₃),0.139 (s, 3H, TBS CH₃), 0.615 (qd, J=8.1, 2.1 Hz, 6H, TES CH₂), 0.919(d, J=6.6 Hz, 3H, Me19), 0.948 (t, J=8.1 Hz, 9H, TES CH₃), 0.952 (s, 9H,TBS t-Bu), 1.058 (s, 3H, Me17), 1.197 (s, 3H, Me16), 1.413 (m, 1H,H14α), 1.900 (br s, 3H, Me18), 2.159 (m, 1H), 2.239-2.387 (m, 2H),2.422-2.700 (m, 4H), 3.094 (qd, J=6.6, 6.6 Hz, 1H, H8), 3.954 (dd,J=9.6, 2.7 Hz, 1H, H2), 4.513 (d, J=12.0 Hz, 1H, 1H×BOM), 4.574 (d,J=7.2 Hz, 1H, 1H×BOM), 4.595 (d, J=12.0 Hz, 1H, 1H×BOM), 4.704 (d, J=7.2Hz, 1H, 1H×BOM), 4.821 (br t, J=8.4 Hz, 1H, H13), 4.848 (s, 1H, H10),4.905 (br s, 1H, 1×H20), 5.029 (br s, 1H, 1×H20), 7.278-7.360 (m,5H×BOM), 9.724 (t, J=1.5 Hz, 1H, CHO).

[0135] Alkene 18. A 0.08 M solution of BaO in MeOH (10.0 mL) was addedto keto aldehyde 17 (116.8 mg, 0.167 mmol) at room temperature under N₂.After stirring at room temperature for 9 h, the solution wasconcentrated under reduced pressure. Then 30 mL of EtOAc and 20 mL of asaturated aqueous NaHCO₃ solution were added. The organic layer wasseparated, and the aqueous layer was extracted with EtOAc (30 mL, 5times). The organic layers were combined and dried over Na₂SO₄. Removalof the solvent gave 110.0 mg (94% yield) of the crude product as a paleyellow oil, which was used without further purification.

[0136] To a solution of the above crude product (110.0 mg, 0.158 mmol)in 2 mL of pyridine at 0° C. under N₂ was added TESOTf (0.11 mL, 0.47mmol). After stirring at 0° C. for 1 h, the solution was diluted with 30mL of 10% EtOAc in hexane, and poured into 30 mL of a saturated aqueousNaHCO₃ solution. The organic layer was separated, and the aqueous layerwas extracted with 10% EtOAc in hexane (30 mL, 3 times). The organiclayers were combined and dried over Na₂SO₄. Removal of the solventfollowed by flash chromatography purification (2% EtOAc/hexane) gave100.0 mg (78% overall yield from hydroxy ketone 16) of the desiredalkene 18 as a colorless oil.

[0137] 18: ¹H NMR (500 MHz, CDCl₃): δ (ppm) 0.099 (s, 3H, TBS CH₃),0.131 (s, 3H, TBS CH₃), 0.565 (q, J=8.0 Hz, 6H, TES CH₂), 0.635 (qd,J=8.0, 2.5 Hz, 6H, TES CH₂), 0.925 (s, 9H, TBS t-Bu), 0.943 (t, J=8.0Hz, 9H, TES CH₃), 0.960 (s, 3H, Me17), 0.995 (t, J=8.0 Hz, 9H, TES CH₃),1.136 (s, 3H, Me19), 1.155 (s, 3H, Me16), 1.561 (m, 1H, H6β), 1.637 (dd,J=15.0, 5.5 Hz, 1H, H14α), 1.794 (br d, J=9.0 Hz, 1H, H1), 1.915 (m, 1H,H6α), 2.043 (d, J=1.5 Hz, 3H, Me18), 2.106-2.162 (m, 2H, 2×H5), 2.500(dt, J=15.0, 9.0 Hz, 1H, H14β), 3.244 (br d, J=4.0 Hz, 1H, H3), 3.785(br dd, J=4.0, 1.0 Hz, 1H, H2β), 4.173 (dd, J=11.0, 4.5 Hz, 1H, H7α),4.565 (m, 1H, H13β), 4.579 (s, 2H, 2H×BOM), 4.680 (d, J=7.0 Hz, 1H,1H×BOM), 4.703 (d, J=7.0 Hz, 1H, 1H×BOM), 4.929 (br s, 1H, 1×H20), 5.363(s, 1H, H10α), 5.489 (t, J=2.0 Hz, 1H, 1×H20), 7.270-7.343 (m, 5H,5H×BOM); ¹³C NMR (75 MHz, CDCl₃): δ (ppm) −5.33, −4.54, 4.89, 5.92,6.62, 6.71, 11.53, 17.27, 17.78, 24.95, 25.65, 31.09, 32.40, 32.79,37.63, 37.83, 47.44, 49.34, 62.19, 68.53, 70.05, 75.00, 76.36, 78.90,93.74, 113.68, 127.73, 127.90, 128.54, 136.72, 137.17, 138.11, 143.93,209.62.

[0138] Allylic alcohol 19. To a solution of alkene 18 (80.0 mg, 0.0985mmol) in 5 mL of CH₂Cl₂ at room temperature under N₂ was added 1.0 mL oft-BuOOH (90% pure, 9.8 mmol), followed by SeO₂ (109.0 mg, 0.985 mmol).After stirring at room temperature for 10 h, the solution was dilutedwith 50 mL of 20% EtOAc in hexane and poured into 20 mL of a saturatedaqueous NaHCO₃ solution. The organic layer was separated and the aqueouslayer was extracted with 20% EtOAc in hexane (20 mL, 3 times). Theorganic layers were combined and washed with 10 mL of water, and thendried over Na₂SO₄. Removal of the solvent followed by flashchromatography purification (3% EtOAc/hexane) gave 75.0 mg (92% yield)of the desired allylic alcohol 19 as a colorless oil.

[0139] 19: ¹H NMR (500 MHz, CDCl₃): δ (ppm) 0.135 (s, 3H, TBS CH₃),0.162 (s, 3H, TBS CH₃), 0.571 (q, J=8.0 Hz, 6H, TES CH₂), 0.640 (qd,J=8.0, 1.5 Hz, 6H, TES CH₂), 0.927 (s, 3H, Me17), 0.943 (s, 9H, TBSt-Bu), 0.959 (t, J=8.0 Hz, 9H, TES CH₃), 0.995 (t, J=8.0 Hz, 9H, TESCH₃), 1.109 (s, 3H, Me19), 1.163 (s, 3H, Me16), 1.564-1.632 (m, 2H, H6β,H14α), 1.792 (br d, J=8.5 Hz, 1H, H1), 2.108 (br, 1H, OH5), 2.123 (d,J=1.0 Hz, 3H, Me18), 2.155 (m, 1H, H6α), 2.550 (dt, J=15.0, 8.5 Hz, 1H,H14β), 3.785 (br d, J=2.0 Hz, 1H, H2β), 3.931 (br t, J=2.0 Hz, 1H, H3),4.180 (t, J=3.0 Hz, 1H, H5β), 4.570 (s, 2H, 2H×BOM), 4.597 (dd, J=11.5,4.5 Hz, 1H, H7α), 4.613 (br t, J=8.5 Hz, 1H, H13β), 4.675 (d, J=7.0 Hz,1H, 1H×BOM), 4.697 (d, J=7.0 Hz, 1H, 1H×BOM), 5.166 (t, J=2.0 Hz, 1H,1×H20), 5.414 (s, 1H, H10α), 5.742 (t, J=2.0 Hz, 1H, 1×H20), 7.268-7.347(m, 5H, 5H×BOM).

[0140] Diol mesylate 20. To a solution of allylic alcohol 19 (14.0 mg,0.017 mmol) in 0.7 mL of pyridine at 0° C. under N₂ was added MsCl (0.05mL, 0.645 mmol). The solution was stirred at 0° C. for 2 h. Then 1.5 mLof Et₂O followed by 0.22 mL (0.034 mmol) of a 0.157 M solution of OsO₄in THF was added. The mixture was kept at −20° C. for 12 h, and then wasdiluted with 5 mL of THF. Next, 30 mg of NaHSO₃ followed by 0.5 mL ofH₂O was added. After stirring at room temperature for 8 h, the solutionwas diluted with 50 mL of EtOAc, and poured into 50 mL of a saturatedaqueous NaHCO₃ solution. The organic layer was separated, and theaqueous layer was extracted with EtOAc (20 mL, 3 times). The organiclayers were combined and dried over Na₂SO₄. Removal of the solvent gave15 mg of desired diol mesylate 20 as a pale yellow oil, which was usedwithout further purification.

[0141] 20: ¹H NMR (500 MHz, CDCl₃): δ (ppm) 0.122 (s, 3H, TBS CH₃),0.173 (s, 3H, TBS CH₃), 0.558 (q, J=8.0 Hz, 6H, TES CH₂), 0.640 (qd,J=8.0, 5.0 Hz, 6H, TES CH₂), 0.949 (t, J=8.0 Hz, 9H, TES CH₃), 0.964 (s,9H, TBS t-Bu), 0.978 (t, J=8.0 Hz, 9H, TES CH₃), 1.070 (s, 3H, Me16),1.085 (s, 3H, Me17), 1.174 (s, 3H, Me19), 1.935 (m, 1H, H6β),1.977-2.037 (m, 2H, H14α, H1), 2.123 (d, J=1.0 Hz, 3H, Me18), 2.244 (dt,J=15.0, 4.5 Hz, 1H, H6α), 2.316 (dt, J=14.0, 9.0 Hz, 1H, H14β), 2.381(dd, J=10.5, 1.5 Hz, 1H, OH20), 3.147 (s, 3H, SO₂CH₃), 3.575 (d, J=6.5Hz, 1H, H3), 3.607 (t, J=10.5 Hz, 1H, 1×H20), 3.940 (dd, J=10.5, 1.5 Hz,1H, 1×H20), 3.990 (dd, J=6.5, 2.5 Hz, 1H, H2β), 4.133 (s, 1H, OH4),4.228 (dd, J=11.5, 4.5 Hz, 1H, H7α), 4.613 (s, 2H, 2H×BOM), 4.766 (d,J=7.0 Hz, 1H, 1H×BOM), 4.825 (m, 1H, H13β), 4.839 (d, J=7.0 Hz, 1H,1H×BOM), 4.895 (m, 1H, H5β), 5.276 (s, 1H, H10α), 7.298-7.357 (m, 5H,5B×BOM).

[0142] Oxetane 21. To a solution of the above diol mesylate 20 in 1.0 mLof toluene at room temperature under N₂ was added DBU (0.06 mL, 0.04mmol). The solution was then heated to 120° C. (oil bath temperature)for 15 minutes, and kept at 120° C. for another 15 minutes. Removal ofthe solvent followed by flash chromatography purification (15%EtOAc/hexane) gave 12.5 mg of desired oxetane 21 (87% overall yield fromallylic alcohol 19) as a colorless oil.

[0143] 21: ¹H NMR (500 MHz, CDCl₃): δ (ppm) 0.143 (s, 3H, TBS CH₃),0.154 (s, 3H, TBS CH₃), 0.580 (q, J=8.0 Hz, 6H, TES CH₂), 0.635 (qd,J=8.0, 2.5 Hz, 6H, TES CH₂), 0.952 (t, J=8.0 Hz, 9H, TES CH₃), 0.971 (s,9H, TBS t-Bu), 0.977 (s, 3H, Me17), 0.992 (t, J=8.0 Hz, 9H, TES CH₃),1.116 (s, 3H, Me16), 1.532 (s, 3H, Me19), 1.944 (m, 1H, H1), 1.945 (d,J=1.5 Hz, 3H, Me18), 2.000 (m, 1H, H14α), 2.030 (m, 1H, H6β), 2.407 (dt,J=15.5, 9.5 Hz, 1H, H14β), 2.465 (m, 1H, H6α), 2.990 (s, 1H, OH4), 3.050(d, J=5.5 Hz, 1H, H3), 3.888 (dd, J=5.5, 2.5 Hz, 1H, H2β), 4.042 (dd,J=11.5, 6.5 Hz, 1H, H7α), 4.358 (d, J=8.0 Hz, 1H, H20α), 4.513 (d,J=12.0 Hz, 1H, 1H×BOM), 4.555 (ddd, J=9.5, 4.5, 1.5 Hz, 1H, H13β), 4.608(d, J=12.0 Hz, 1H, 1H×BOM), 4.640 (d, J=8.0 Hz, 1H, H20β), 4.645 (d,J=6.5 Hz, 1H, 1H×BOM), 4.713 (d, J=6.5 Hz, 1H, 1H×BOM), 4.730 (dd,J=10.0, 4.0 Hz, 1H, H5α), 5.153 (s, 1H, H10α), 7.270-7.355 (m, 5H,5H×BOM); ¹³C NMR (75 MHz, CDCl₃): δ (ppm) −5.21, −4.39, 4.99, 5.77,6.60, 6.68, 10.32, 16.28, 17.98, 24.45, 25.84, 30.73, 31.31, 37.53,37.68, 45.36, 50.59, 58.88, 68.15, 70.28, 73.33, 74.74, 76.30, 78.73,81.39, 86.61, 94.82, 127.69, 128.01, 128.69, 136.43, 137.67, 137.83,207.89.

[0144] Diol 22. To a solution of oxetane 21 (60.0 mg, 0.071 mmol) in 0.1mL of CH₃CN at room temperature was added 1.0 mL of a 48%HF/pyridine/CH₃CN (1:3.5:3.5) solution. After stirring at roomtemperature for 24 h, the solution was diluted with 50 mL of EtOAc, andpoured into 20 mL of a saturated aqueous NaHCO₃ solution. The organiclayer was separated, and the aqueous layer was extracted with EtOAc (20mL, 3 times). The organic layers were combined and dried over Na₂SO₄.Removal of the solvent then gave the tetraol as a pale yellow oil, whichwas used without any further purification.

[0145] To a solution of the above oil in 1 mL of pyridine at roomtemperature was added TESCl (0.06 mL, 0.355 mmol). After stirring atroom temperature for 21 h, the solution was diluted with 10 mL of EtOAc,and poured into 20 mL of a saturated aqueous NaHCO₃ solution. Theorganic layer was separated, and the aqueous layer was extracted withEtOAc (20 mL, 3 times). The organic layers were combined and dried overNa₂SO₄. Removal of the solvent followed by chromatography purification(5% EtOAc/hexane) gave the desired diol 22 (48.0 mg, 93% overall yield)as a colorless oil.

[0146] 22: ¹H NMR (500 MHz, CDCl₃): δ (ppm) 0.538 (qd, J=8.0, 1.0 Hz,6H, TES CH₂), 0.707 (q, J=8.0 Hz, 6H, TES CH₂), 0.919 (t, J=8.0 Hz, 9H,TES CH₃), 1.001 (s, 3H, Me17), 1.011 (s, 3H, Me16), 1.026 (t, J=8.0 Hz,9H, TES CH₃), 1.605 (s, 3H, Me19), 1.964-2.037 (m, 3H, H1, H14α, H6β),2.019 (d, J=1.5 Hz, 3H, Me18), 2.392 (m, 1H, H6α), 2.452 (m, 1H, H14β),3.090 (d, J=6.0 Hz, 1H, H3), 3.150 (s, 1H, OH4), 3.873 (dd, J=6.0, 3.0Hz, 1H, H2), 3.988 (dd, J=11.5, 7.5 Hz, 1H, H7α), 4.140 (d, J=3.0 Hz,1H, OH10), 4.396 (d, J=7.5 Hz, 1H, H20α), 4.527 (d, J=11.5 Hz, 1H,1H×BOM), 4.599 (br m, 1H, H13β), 4.621 (d, J=11.5 Hz, 1H, 1H×BOM), 4.626(d, J=7.5 Hz, 1H, H20β), 4.656 (d, J=6.5 Hz, 1H, 1H×BOM), 4.729 (d,J=6.5 Hz, 1H, 1H×BOM), 4.787 (dd, J=9.5, 4.0 Hz, 1H, H5α), 5.106 (d,J=3.0 Hz, 1H, H10), 7.284-7.363 (m, 5H, 5H×BOM); ¹³C NMR (75 MHz,CDCl₃): δ (ppm) 4.672, 4.945, 6.433, 6.645, 9.878, 16.509, 23.976,29.500, 30.775, 31.791, 37.406, 45.222, 50.655, 58.288, 68.259, 70.292,73.494, 74.754, 75.133, 78.639, 81.158, 86.804, 94.907, 127.687,128.067, 128.704, 136.337, 137.597, 140.025, 212.474.

[0147] Bis-acetate 23. To a solution of diol 22 (5.0 mg, 0.007 mmol) in0.5 mL of pyridine at room temperature was added 4-dimethylaminopyridine(2.0 mg, 0.014 mmol) followed by Ac₂O (0.01 mL, 0.1 mmol). Afterstirring at room temperature for 21 h, the solution was diluted with 10mL of EtOAc, and poured into 20 mL of a saturated aqueous NaHCO₃solution. The organic layer was separated, and the aqueous layer wasextracted with EtOAc (20 mL, 3 times). The organic layers were combinedand dried over Na₂SO₄. Removal of the solvent followed by flashchromatography purification (5% EtOAc/hexane) gave the desiredbis-acetate 23 (3.4 mg, 60% yield) as a colorless oil.

[0148] 23: ¹H NMR (500 MHz, CDCl₃): δ (ppm) 0.518 (q, J=8.0, 1.0 Hz, 6H,TES CH₂) 0.600 (qd, J=8.0, 5.0 Hz, 6H, TES CH₂), 0.912 (t, J=8.0 Hz, 9H,TES CH₃), 0.951 (t, J=8.0 Hz, 9H, TES CH₃), 1.042 (s, 3H, Me17), 1.109(s, 3H, Me16), 1.484 (m, 1H, H14α), 1.653 (s, 3H, Me19), 1.918(ddd,J=14.0, 10.5, 2.5 Hz, 1H, H6β), 2.107 (d, J=1.0 Hz, 3H, Me18), 2.138 (s,3H, OAc10), 2.162-2.207 (m, 2H, H1, H14β), 2.538 (m, 1H, H6α), 2.626 (s,3H, OAc4), 3.628 (d, J=6.5 Hz, 1H, H3), 3.999 (dd, J=6.5, 2.5 Hz, 1H,H2), 4.496 (d, J=12.0 Hz, 1H, 1H×BOM), 4.538 (d, J=8.5 Hz, 1H, H20β),4.578-4.627 (m, 3H, H7α, H20α, 1H×BOM), 4.652 (d, J=6.5 Hz, 1H, 1H×BOM),4.709 (m, 1H, H13β), 4.733 (d, J=6.5 Hz, 1H, 1H×BOM), 4.943 (dd, J=9.5,2.5 Hz, 1H, H5β), 6.394 (s, 1H, H10), 7.284-7.369 (m, 5H, 5H×BOM).

[0149] 1-Deoxy-baccatin III. To a solution of bis-acetate 23 (3.4 mg,0.0042 mmol) in 0.5 mL of EtOAc and 0.5 mL of t-BuOH at room temperaturewas added 4.0 mg of 10% Pd on carbon. After stirring under H₂ for 45min., the mixture was diluted with 10 mL of EtOAc, and filtered througha short pad of celite. Removal of the solution gave a colorless oil,which was then dissolved in 0.5 mL of CHCl₃, and loaded onto a column(silica gel). After 2 h at room temperature, the column was washed withEtOAc. Removal of the solvent then gave the desired crude product, whichwas used without any further purification.

[0150] To a solution of the above crude product in 0.5 mL of pyridine atroom temperature was added 4-pyrrolidino-pyridine (1.8 mg, 0.012 mmol)followed by 0.5 mL (0.5 mmol) of a 1.0 M solution of BzCl in pyridine(0.5 mL). After stirring at room temperature for 26 h, the solution wasdiluted with 10 mL of EtOAc, and poured into 20 mL of a saturatedaqueous NaHCO₃ solution. The organic layer was separated, and theaqueous layer was extracted with EtOAc (20 mL, 3 times). The organiclayers were combined and dried over Na₂SO₄. Removal of the solvent thengave the crude benzoate, which was used without any furtherpurification.

[0151] To a solution of the above crude benzoate in 0.1 mL of CH₃CN atroom temperature was added 0.5 mL of a 48% HF/pyridine/CH₃CN (1:3.5:3.5)solution. After stirring at room temperature for 27 h, the solution wasdiluted with 10 mL of EtOAc, and poured into 20 mL of a saturatedaqueous NaHCO₃ solution. The organic layer was separated, and theaqueous layer was extracted with EtOAc (10 mL, 3 times). The organiclayers were combined and dried over Na₂SO₄. Removal of the solventfollowed by flash chromatography purification (60% EtOAc/hexane) gavethe desired 1-deoxy-baccatin III (1.4 mg, 59% overall yield frombis-acetate 23).

[0152] 1-Deoxy-baccatin III: ¹H NMR (500 MHz, CDCl₃): δ (ppm) 1.069 (s,3H, Me17), 1.204 (s, 3H, Me16), 1.667 (s, 3H, Me19), 1.730 (ddd, J=15.0,7.5, 1.0 Hz, 1H, H14α), 1.890 (ddd, J=15.0, 6.0, 2.0 Hz, 1H, H6β), 1.978(d, J=5.5 Hz, 1H, OH13), 2.034 (ddd, J=9.0, 3.5, 1.0 Hz, 1H, H1), 2.085(d, J=1.0 Hz, 3H, Me18), 2.227 (s, 3H, OAc10), 2.290 (s, 3H, OAc4),2.387 (d, J=4.5 Hz, 1H, OH7), 2.516 (ddd, J=15.0, 10.0, 9.0 Hz, 1H,H14β), 2.583 (ddd, J=15.0, 10.0, 7.0 Hz, 1H, H6α), 3.738 (d, J=6.5 Hz,1H, H3α), 4.156 (dd, J=8.5, 1.0 Hz, 1H, H20β), 4.373 (d, J=8.5 Hz, 1H,H20α), 4.471 (ddd, J=10.0, 7.0, 4.5 Hz, 1H, H7α), 4.712 (dddd, J=10.0,7.5, 5.5, 1.0 Hz, 1H, H13β), 5.023 (ddd, J=9.5, 2.0, 1.0 Hz, 1H, H5α),5.643 (dd, J=6.5, 3.5 Hz, 1H, H2β), 6.320 (s, 1H, H10α), 7.472 (t, J=8.0Hz, 2H, benzoate-m), 7.597 (dd, J=8.0, 1.0 Hz, 1H, benzoate-p), 8.085(dd, J=8.0, 1.0 Hz, 2H, benzoate-o).

[0153] In view of the above, it will be seen that the several objects ofthe invention are achieved.

[0154] As various changes could be made in the above compositionswithout departing from the scope of the invention, it is intended thatall matter contained in the above description be interpreted asillustrative and not in a limiting sense.

What we claim is:
 1. A process for the preparation of an intermediate useful in the synthesis of 1-deoxy baccatin III, 1-deoxy taxol or 1-deoxy taxol analogs comprising at least one of the following steps: (a) reacting a compound having the formula:

with a vinyl organometallic reagent to form a compound having the formula:

(b) reacting a compound having the formula:

with a paladium catalyst to form a compound having the formula:

(c) reacting a compound having the formula:

with a base, most preferably BaO in methanol, and protecting the C7 hydroxy substituent, for example, by reacting the product with TESOTf, to form a compound having the formula:

(d) reacting a compound having the formula:

with SeO₂ to form a compound having the formula:

wherein E₇ is hydrogen or a hydroxy protecting group, and P₂, P₇, P₉, P₁₀ and P₁₃ are hydroxy protecting groups.
 2. A compound having the formula:

wherein M comprises ammonium or is a metal; R₂ is —OT₂, —OCOZ₂, or —OCOOZ₂; R₄ is —OT₄, —OCOZ₄, or —OCOOZ₄; R₆ is hydrogen, keto, —OT₆, —OCOZ₆ or —OCOOZ₆; R₇ is hydrogen, halogen, —OT₇, —OCOZ₇ or —OCOOZ₇; R₉is hydrogen, keto, —OT₉, —OCOZ₉ or —OCOOZ₉; R₁₀ is hydrogen, keto, —OT₁₀, —OCOZ₁₀ or —OCOOZ₁₀; R₆, R₇, R₉, and R₁₀ independently have the alpha or beta stereochemical configuration; R₁₃ is keto, MO—, hydroxy, protected hydroxy, or

T₂, T₄, T₆, T₇, T₉ and T₁₀ are independently hydrogen or hydroxy protecting group; X₁ is —OX₆; X₂ is hydrogen, hydrocarbon, heterosubstituted hydrocarbon, or heteroaryl; X₃ and X₄ are independently hydrogen, hydrocarbon, heterosubstituted hydrocarbon, or heteroaryl; X₅ is —COX₁₀, —COOX₁₀, —COSX₁₀, or —CONX₈X₁₀; X₆ is hydrogen, hydrocarbon, heterosubstituted hydrocarbon, heteroaryl, or hydroxy protecting group or a functional group which increases the water solubility of the taxane derivative; X₈ is hydrogen, hydrocarbon, heterosubstituted hydrocarbon; X₁₀ is hydrocarbon, heterosubstituted hydrocarbon, or heteroaryl; and Z₂, Z₄, Z₆, Z₇, Z₉ and Z₁₀ are independently hydrocarbon, heterosubstituted hydrocarbon, or heteroaryl.
 3. The compound of claim 2 wherein R₁₀ is hydrogen or keto.
 4. The compound of claim 2 wherein R₁₀ is hydroxy, protected hydroxy, or —OCOZ₁₀, and Z₁₀ is alkyl, substituted alkyl, phenyl, substituted phenyl, or heteroaryl.
 5. The compound of claim 2 wherein R₉ is hydrogen, β-hydroxy, β-protected hydroxy or —OCOZ₉, and Z₉ is alkyl, substituted alkyl, phenyl, substituted phenyl, or heteroaryl.
 6. The compound of claim 2 wherein R₉ is keto.
 7. The compound of claim 2 wherein R₇ is hydrogen, halogen or —OCOZ₇, and Z₇ is alkyl, substituted alkyl, phenyl, substituted phenyl, or heteroaryl.
 8. The compound of claim 2 wherein R₇ is hydroxy or protected hydroxy.
 9. The compound of claim 2 wherein R₆ is hydrogen.
 10. The compound of claim 2 wherein R₆ is —OCOZ₆ or —OCOOZ₆, and Z₆ is as defined in claim
 2. 11. The compound of claim 2 wherein R₄ is hydroxy, protected hydroxy or —OCOOZ₄, and Z₄ is as defined in claim
 2. 12. The compound of claim 2 wherein R₄ is —OCOZ₄, and Z₄ is phenyl, substituted phenyl, or heteroaryl.
 13. The compound of claim 2 wherein R₂ is hydroxy, protected hydroxy or —OCOOZ₂, and Z₂ is as defined in claim
 2. 14. The compound of claim 2 wherein R₂ is —OCOZ₂, and Z₂ is alkyl, substituted alkyl, phenyl, substituted phenyl, or heteroaryl.
 15. The compound of claim 2 wherein R₁₃ is hydroxy or protected hydroxy.
 16. The compound of claim 2 wherein R₁₃ is MO—, and M is as defined in claim
 2. 17. The compound of claim 2 wherein R₁₃ is

and X₁, X₂, X₃, X₄ and X₅ are as defined in claim
 2. 18. The compound of claim 17 wherein X₅ is —COX₁₀ or —COOX₁₀, and X₁₀ is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, or heteroaryl.
 19. The compound of claim 17 wherein X₅ is —CONX₈X₁₀ and X₈ and X₁₀ are as defined in claim
 2. 20. The compound of claim 17 wherein X₁₀ is heteroaryl.
 21. The compound of claim 17 wherein X₃ is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, or heteroaryl; and X₄ is hydrogen.
 22. The compound of claim 21 wherein X₃ is substituted, unsubstituted, straight, branched chain or cyclic propyl.
 23. The compound of claim 21 wherein X₃ is heteroaryl.
 24. The compound of claim 2 wherein R₉ is hydroxy, protected hydroxy or keto, R₁₀ is —OCOZ₁₀, and Z₁₀ is as defined in claim
 2. 25. The compound of claim 2 wherein R₉ is hydrogen and R₁₀ is keto.
 26. The compound of claim 2 wherein R₉ is keto and R₁₀ is hydrogen.
 27. The compound of claim 2 wherein R₉ is hydroxy or protected hydroxy, and R₁₀ is hydroxy or protected hydroxy.
 28. The compound of claim 2 wherein R₉ is β-hydroxy or β-protected hydroxy, R₁₀ is —OCOZ₁₀, and Z₁₀ is as defined in claim
 2. 29. The compound of claim 2 wherein R₉ is —OCOZ₉, R₁₀ is hydroxy or protected hydroxy, and Z₉ is as defined in claim
 2. 30. The compound of claim 2 wherein R₂ is —OCOZ₂, R₄ is —OCOZ₄, hydroxy or protected hydroxy, and Z₂ and Z₄ are as defined in claim
 2. 31. The compound of claim 2 wherein R₂ is —OCOZ₂; R₄ is —OCOZ₄; R₇ is hydroxy or protected hydroxy; R₉ is keto; R₁₀ is hydroxy, protected hydroxy or —OCOZ₁₀; and Z₂, Z₄ and Z₁₀ are as defined in claim
 2. 32. The compound of claim 31 wherein R₂ is benzoyloxy and R₄ is acetoxy.
 33. The compound of claim 2 wherein R₂ is —OCOZ₂; R₇ is hydroxy or protected hydroxy; R₉ is keto; and Z₂ is as defined in claim
 2. 34. The compound of claim 2 wherein R₄ is —OCOZ₄; R₇ is hydroxy or protected hydroxy; R₉ is keto; and Z₄ is as defined in claim
 2. 35. The compound of claim 2 wherein R₂ is keto and R₇ is hydroxy or protected hydroxy.
 36. The compound of claim 2 wherein R₂ is benzoyloxy; R₄ is acetoxy; R₆ is hydrogen; R₇ is hydroxy or protected hydroxy; R₉ is keto; R₁₀ is hydroxy, protected hydroxy or acetoxy; and R₁₃ is hydroxy or protected hydroxy.
 37. The compound of claim 2 that is 1-deoxy taxol.
 38. A compound selected from the group consisting of:

wherein R₉ is hydrogen, hydroxy or protected hydroxy; and R₁₀ is hydroxy, protected hydroxy or keto;

wherein R₁₀ is hydroxy or protected hydroxy;

wherein R₂ is hydrogen, hydroxy or protected hydroxy; R₉ is hydroxy or protected hydroxy; R₁₀ is hydroxy or protected hydroxy; and R₁₃ is hydroxy or protected hydroxy;

wherein R₃ is hydroxy or protected hydroxy; R₉ is hydroxy or protected hydroxy; R₁₀ is hydroxy or protected hydroxy; and R₁₃ is hydroxy or protected hydroxy;

wherein R₂ is hydroxy or protected hydroxy, or together with R₃ forms a carbonate; R₃ is hydrogen, hydroxy or protected hydroxy, or together with R₂ forms a carbonate; R₇ is hydroxy, protected hydroxy or keto; R₉ is hydroxy, protected hydroxy or keto; R₁₀ is hydroxy or protected hydroxy; and R₁₃ is hydroxy or protected hydroxy;

wherein R₂ is hydroxy or protected hydroxy; R₄ is hydroxy or protected hydroxy, or together with R_(4a) forms a keto; R_(4a) is —CH₂OH or together with R₄ forms a keto; R₅ is hydroxy, protected hydroxy or CH₃SO₂—; R₇ is hydroxy or protected hydroxy; R₁₀ is hydroxy or protected hydroxy; and R₁₃ is hydroxy or protected hydroxy; and

wherein R₂ is hydroxy or protected hydroxy; R₄ is hydroxy, protected hydroxy or acetoxy; R₇ is hydroxy or protected hydroxy; R₁₀ is hydroxy, protected hydroxy or acetoxy; and R₁₃ is hydroxy or protected hydroxy. 